Manufacturing system for biopharmaceutical products

ABSTRACT

The present disclosure relates to a manufacturing system, method and control circuitry for quality assured manufacturing of at least two biopharmaceutical products. The manufacturing system comprises a warehouse facility, a hydration facility, and at least two biopharmaceutical manufacturing facilities, wherein the warehouse facility and hydration facility are comprised in the macro structure. Each biopharmaceutical manufacturing facility is comprised in a respective micro node, and a control facility in the macro structure is configured to control interoperability of the macro structure and the micro nodes by means of a network spine interconnecting the macro structure with each micro node.

TECHNICAL FIELD

The present disclosure relates to a manufacturing system and method forquality assured manufacturing of biopharmaceutical products.

BACKGROUND ART

The development of novel biopharmaceutical compounds typically requireslarge investments in time and capital to translate scientific discoveryinto new medicine and to build specialized manufacturing facilities andequipment. Advanced technologies drive biopharmaceutical manufacturingthat aligns with research and development, and requires considerablescientific know-how and infrastructure.

Over the past decade, improvements in biopharmaceutical manufacturingprovide an ability to create and maintain market access through scalableand flexible operations, controlled costs, and high quality. In recentyears the industry has increasingly turned its attention towardimprovements in manufacturing technologies. Emerging technologies aregenerating further changes across the biopharmaceutical workforce andimpacting manufacturers' collaboration strategies and their choices offacility locations.

The past decade has seen a significant shift in the nature of theproducts being manufactured and sold by the innovative biopharmaceuticalindustry. The global biopharmaceutical portfolio of today reflects agreater prevalence of large molecule drugs, expansion in the number ofpersonalized or targeted products, and a rise of treatments for manyorphan diseases. These development trends provide for biopharmaceuticalproducts with extremely limited production runs, highly specificmanufacturing requirements, and genotype-specific products. The on-goingshift in the product mix provides a need for continuous improvement ofthe efficiency and effectiveness of production biopharmaceuticalmanufacturing.

Biologic medicines such as vaccines are complex molecules made by orfrom living cells and are often infused or injected. As such, theyrequire highly specialized manufacturing, special storage and handling,and a tightly controlled, high quality manufacturing and distributionnetwork to ensure safety and effectiveness. Developments are alsoobserved with regard to orphan drugs, i.e., drugs aimed at diseases withpatient populations of under 200,000, and there has been a steadyincrease over the past decade. Furthermore, manufacturers areincreasingly focusing on more complex diseases for which there are fewor no effective treatments. New treatments for these diseases arecharacterized by small volume products. Orphan drugs have created theneed for manufacturing flexibility and the ability to use equipment, andsupplies more efficiently and for more than one product because of theirrelatively small volumes. Additionally, orphan drugs have put pressureon manufacturing volume management, as production processes can oftenyield larger batches than the required volumes.

Another important trend within biopharmaceuticals is the emergence ofpersonalized medicine; products that target a specific population ofpatients. Over time, as patient-level personalized medicines areintroduced, manufacturing and product supply complexity will likelyincrease. Furthermore, manufacturing processes will need to accommodatesmall or scale batch specificity.

These drug portfolio trends have contributed to an increase in thenumber and complexity of products being manufactured and sold. They haveresulted in greater product variety and increased occurrences ofsmall-volume runs, which require frequent changeovers and maynecessitate equipment reconfigurations and updates. Additionally, thenew medicines have increased the need for more complex manufacturingprocesses, more advanced equipment, and cold chain or controlledstorage. Overall, these drug portfolio trends indicate that there is aneed for improved manufacturing creating flexibility with uncompromisedquality, while creating operating efficiencies that can help reducecosts.

SUMMARY OF THE INVENTION

An object of the present disclosure is to provide solutions which seekto mitigate, alleviate, or eliminate one or more of the above-identifieddeficiencies in the art and to provide improved biopharmaceuticalmanufacturing.

This object is obtained by a manufacturing system for quality assuredmanufacturing of at least two biopharmaceutical products, themanufacturing system comprising a warehouse facility, a hydrationfacility, and at least two biopharmaceutical manufacturing facilities.The warehouse facility and hydration facility are comprised in a macrostructure and each biopharmaceutical manufacturing facility is comprisedin a respective micro node. A control facility in the macro structure isconfigured to control interoperability of the macro structure and themicro nodes by means of a network spine interconnecting the macrostructure with each micro node.

The proposed manufacturing system provides for improved use of resourcesand reduced environmental impact for manufacturing of at least twobiopharmaceutical products, e.g., biopharmaceutical drugs, whilstmaintaining quality assurance and independence in each manufacturingprocess.

According to an aspect of the disclosure, the macro structure and eachmicro node respectively each comprise a communication interface to thenetwork spine.

According to an aspect of the disclosure, each micro node, which issupported by the macro structure by means of the network spine, isself-sufficient and independent of the other micro nodes.

According to a further aspect of the disclosure, each micro node isinter-operationally discrete from the other micro nodes.

Advantages of setting up a manufacturing system with self-sufficient,independent and inter-operationally discrete micro nodes communicativelyconnected to a macro structure comprises improved security, scalability,reduced environmental impact and energy requirements. Other benefits arelowered capital and operating costs as well as enhanced quality.

The object of the disclosure is also obtained by a method for qualityassured manufacturing of at least two biopharmaceutical products in amanufacturing system, the manufacturing system comprising a macrostructure, at least two micro nodes and a network spine interconnectingthe macro structure with each micro node. The macro structure comprisesa warehouse facility and a hydration facility. The at least two micronodes representing inter-operationally discrete biopharmaceuticalmanufacturing facilities, wherein a control facility in the macrostructure is configured to control interoperability of the macrostructure and the micro nodes by means of the network spine. The methodcomprises to obtain, in the respective micro nodes, supply materialscomprising customized culture media in single-use equipment from themacro structure by means of the network spine. The supply materials toproduce respective biopharmaceutical products are processed inrespective micro nodes.

The object of the disclosure is also obtained by a computer programproduct comprising at least one non-transitory computer readable storagemedium having computer-executable program code instructions storedtherein. The computer-executable program code instructions compriseprogram code instructions configured, when executed in a controlfacility of a macro structure, to receive, from a micro node, acommunication comprising an order for supply materials, wherein thecustomized supply materials comprise customized culture media. Thecomputer-executable program code instructions further comprise programcode instructions configure to, when executed in a control facility of amacro structure, prepare the customized culture media and send thecustomized culture media in single-use equipment from the macrostructure to the micro node by means of a network spine interconnectingthe macro structure with the micro node.

In addition to the advantages mentioned above, which of course also areapplicable to the method and computer program product embodiments, thedisclosure provides the advantage of improved process robustness and thepossibility for accelerated scale-up to commercial production ofbiopharmaceutical products. Further advantages include increasedflexibility and reduced production lead times.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing will be apparent from the following more particulardescription of the example embodiments, as illustrated in theaccompanying drawings in which like reference characters refer to thesame parts throughout the different views. The drawings are notnecessarily to scale, emphasis instead being placed upon illustratingthe example embodiments.

FIGS. 1-2 are block diagrams of a manufacturing system according tovarious embodiments of the present disclosure;

FIGS. 3 and 4 each provide a flowchart illustrating various processesand procedures that may be completed in accordance with variousembodiments of the present invention;

FIG. 5 is a block diagram illustration of a macro structure controlfacility.

DETAILED DESCRIPTION

Various embodiments of the present invention now will be described morefully hereinafter with reference to the accompanying drawings, in whichsome, but not all embodiments of the invention are shown. The inventionmay be embodied in many different forms and should not be construed aslimited to the embodiments set forth herein; rather, these embodimentsare provided so that this disclosure will satisfy applicable legalrequirements. Advantages and features of the present disclosure andmethods to achieve them will become apparent from the below descriptionof exemplary embodiments. However, the present disclosure is not limitedto the exemplary embodiments disclosed herein but may be implemented invarious different ways. The exemplary embodiments are provided formaking the disclosure of the present disclosure thorough and for fullyconveying the scope of the present disclosure to those skilled in theart. It is to be noted that the scope of the present disclosure isdefined solely by the claims.

The terminology used herein is for the purpose of describing particularaspects of the disclosure only, and is not intended to limit theinvention. As used herein, the singular forms “a”, “an” and “the” areintended to include the plural forms as well, unless the context clearlyindicates otherwise.

It should be noted that the word “comprising” does not necessarilyexclude the presence of other elements or steps than those listed. Itshould further be noted that any reference signs do not limit the scopeof the claims, that the example embodiments may be implemented at leastin part by means of both hardware and software.

The various example embodiments described herein are described in thegeneral context of method steps or processes, which may be implementedin one aspect by a computer program product, embodied in acomputer-readable medium, including computer-executable instructions,such as program code, executed by computers in networked environments.

Detailed descriptions of well-known functions and structuresincorporated herein will be omitted to avoid obscuring the subjectmatter of the present disclosure. Further, terms or words used in thespecification and claims shall not be construed merely in a conventionaland dictionary definition but shall be construed in a meaning andconcept corresponding to the technical idea of the present invention.

FIG. 1 illustrates an example embodiment of a system architecture thatmay be used in conjunction with various embodiments of the presentinvention for quality assured manufacturing of at least twobiopharmaceutical products. The embodiment illustrated in FIG. 1comprises a warehouse facility 210, a hydration facility 220 and atleast two biopharmaceutical manufacturing facilities. The warehousefacility 210 and the hydration facility 220 are comprised in a macrostructure 200, whereas each manufacturing facility is comprised in arespective micro node 300. A control facility in the macro structure 200is configured to control interoperability of the macro structure 200 andthe micro nodes 300 by means of a network spine 400 interconnecting themacro structure 200 with each micro node 300.

FIG. 2 illustrates a further example embodiment of a system architecturethat may be used in conjunction with various embodiments of the presentinvention for quality assured manufacturing of at least twobiopharmaceutical products. A manufacturing system 100 for qualityassured manufacturing of at least two biopharmaceutical products isdisclosed. The manufacturing system 100 comprises a warehouse facility210, a hydration facility 220, and at least two biopharmaceuticalmanufacturing facilities. The macro structure 200 comprises thewarehouse facility 210 and the hydration facility 220 and a controlfacility 230. The two biopharmaceutical manufacturing facilities arecomprised in a respective micro node 300. The control facility 230 ofthe macro structure 200 is configured to control interoperability of themacro structure 200 and the micro nodes 300 by means of a network spine400 interconnecting the macro structure 200 with each micro node 300.

The macro structure 200 may be operated by the facility provider onbehalf of a biopharmaceutical manufacturer residing in one or more ofthe micro nodes 300, but the macro structure 200 may also be operated byand/or on behalf of a facility provider that has no direct involvementin the biopharmaceutical manufacturing taking place in the micro nodes300.

As mentioned, the macro structure 200 comprises a warehouse facility210, a hydration facility 220 and a control facility 230. According toan aspect of the disclosure, the warehouse facility 210 may includesegregated areas for each biopharmaceutical manufacturer, wherein thesupply material may be stored as well as the final product ready fordelivery. The macro structure 200 may also be configured for utilitysupplies and waste treatment, e.g., power, gas, water and effluents.

The network spine 400 interconnects the macro structure 200 and eachindividual micro node 300. Thus, the manufacturing system 100 isconfigured with a spine approach with micro nodes 300 comprisingbiopharmaceutical manufacturing capability connected to the spine aswell as support facilities forming part of the macro structure 200.According to aspects of the disclosure, the macro structure 200 and eachmicro node 300 comprises a communication interface 410 to the networkspine 400. The micro nodes 300 may be arranged on one side of thenetwork spine 400, while the support facilities are arranged on theother side.

The above disclosed manufacturing system 100 may also be presented at abiopharmaceutical site, comprising biopharmaceutical manufacturingfacilities and support utilities interconnected so that themanufacturing performed in the respective manufacturing facilities isseparated from one another. According to aspects of the disclosure, eachmicro node 300 is self-sufficient and independent of the other micronodes 300. Furthermore, each micro node 300 is inter-operationallydiscrete from the other micro nodes 300. Each micro node 300 maycomprise independent IT systems/server rooms and independent phonesystems. Furthermore, access control will be segregated per micro node300. Each micro node 300 may comprise an independent security system.

As disclosed in FIG. 2, the manufacturing system 100 may initially beset up with two micro nodes 300 a, 300 b that will be operationalimmediately, while the micro nodes 300 c, 300 d are ready to bring intooperation or projected to be brought into operation at a future date. Asindicated in FIG. 2, preparations may also have been made for extendingthe network spine with a future extension or sub-spine 400′ to allowadd-on of further micro-nodes that may not yet have been projected. Aswill be obvious to the person skilled in the art, such sub-spines mayextend in directions orthogonal or at other angles to the establishednetwork spine. The micro nodes 300 a, 300 b comprise respectivebiopharmaceutical manufacturing facilities, including office facilitiesand laboratories dedicated for the specific biopharmaceutical productionof the micro node.

Turning back to the macro structure 200, a warehouse facility 210, ahydration facility 220 and a control facility is comprised in thestructure. The macro structure 200 may also be configured to providesecurity operation common throughout the site, provided by a sitemanager or by an independent company. Likewise, parts of an ITinfrastructure may be common within the site, while other parts remainunder the sole control of a micro node operator. Access control will besegregated per micro node 300, but will of course also be provided withregard to access to the macro structure 200. According to aspects of thedisclosure, access control will be provided in the communicationsinterface to the network spine 400, i.e., in the communicationsinterface 410 between each micro node 300 and the network spine 400,e.g., for a materials air lock that may represent a materials deliveryinterface 412 between the respective micro nodes 300 and the networkspine 400. Transporting of materials to/from the micro nodes 300 overthe network spine 400, may be fully automated using unmanned transportequipment or vehicles to transport materials between the warehousefacility 210 or hydration facility 220 and the manufacturing facility.Common emergency systems will also be provided in the macro structure200, as well as micro node 300 implemented emergency systems. Theseemergency systems provide fulfillment of at least minimum safetyrequirements throughout the whole system. Things to be consideredinclude but are not limited to:

-   -   easy accessibility of safety showers and eyewash stations in all        production areas, laboratories, material handling areas,        mechanical areas and waste storage areas. iii. Fire        extinguishers, first aid cabinets, door release mechanisms, etc.    -   spill containment for flammables/chemical handling areas    -   fire rated areas, with correct egress, sprinkler coverage, and        ventilation.    -   electrical design per the requirements of the electrical        classification for each area of the site, including the        flammables/chemical handling areas.

A common warehouse facility 210 belongs to the key aspects of the macrostructure 200. In the warehouse, segregation may be maintained betweenwarehouse materials of the biopharmaceutical manufacturer residing inthe micro nodes 300 and a common warehouse area. However, even with suchsegregation, access to the warehouse facility 210 may be restricted foroperators of the micro nodes 300, and transportation of materialsbetween a micro node 300 and the warehouse is arranged through thenetwork spine 400. Such material includes finished products, interimproducts and raw materials. Storage of raw materials is carried out inthe warehouse where the material may be stored at the appropriatetemperature, e.g., ambient, 2-8° C., or −20° C. The storage may beperformed segregated per micro node. This may also apply to cell bankingrequired for all the biopharmaceutical manufacturers residing in themicro nodes 300, however cell banking may also be done in laboratoriesset up in the respective micro nodes and from security andcross-contamination aspects there are benefits in only having the cellbanking in the respective micro nodes. Hazardous materials may also beseparated and stored in a different location within the warehouse.Materials that are released or unreleased may be stored alongside eachother as the inventory management system identifies locations of all rawmaterials. Raw Material sampling may occur in a raw material samplingarea directly adjacent to the warehouse. For an initial manufacturingsystem 100 set up with two micro nodes 300 a, 300 b, warehouse areas forthese micro node operators may be outfitted or operational at projectstart-up. Warehouse areas for further micro nodes 300 to beinterconnected to the macro structure 200 at a later occasion will bebuilt but not outfitted. These warehouse areas will only be outfitted oroperational when further micro nodes 300 c-d are contracted. Thewarehouse facility 210 will comprise receiving docks arranged to receivematerial delivered from external source. A materials delivery interfacemay also be provided to the network spine 400 interconnecting the macrostructure 200 with the respective micro nodes 300. The receiving docksmay be arranged adjacent to warehouse and storage to provide an easyflow for materials from the receiving docks into the warehouse ahazardous storage area, quarantine area and raw material sampling lab.

The hydration facility 220 is a key facility of the macro structure 200.The hydration facility 220 should be dimensioned to support at least aplurality of micro nodes 300. It may further be capable of supportingexternal facilities. While the hydration facility 220 is dimensioned tosupport a pre-determined number of micro nodes 300, there is of courseno need for all micro nodes 300 to be introduced in the manufacturingsystem 100 at the time of initiating operation in the system. One ormore micro nodes 300 may easily be retro-fitted to the manufacturingsystem 100 using pre-determined connection points to the network spine400. According to an aspect of the disclosure, the hydration facility220 is configured to receive culture media and buffer material in apowder or concentrate form and to hydrate such material in the hydrationfacility 220. Whilst belonging to the macro structure 200, the hydrationfacility 220 is connected to the network spine 400 to allowtransportation of material to/from the micro nodes 300. According toaspects of the disclosure, the hydration facility 220 will be operatedby personnel separate from that of the micro nodes 300 and thebiopharmaceutical manufacturing facilities of the micro nodes 300 mayreceive materials from the hydration facility 220 in single-usecontainers or other equipment or mechanisms. According to aspects of thedisclosure, the hydration facility 220 comprises at least one water forinjection system, WFI, a process water system, PW, process gases and aneutralization system. The hydration facility may also comprise anautoclave facility and/or a glass washer as optional features. Utilitiesto support the hydration process include chilled water, plant steam, andelectricity. The hydration facility 220 may further include tugs orvehicles for automatically and/or manually moving material into themicro nodes 300 or warehouse facility 210 by means of the network spine400.

A control facility 230 is configured to control interoperability of themacro structure 200 and the micro nodes 300 by means of a network spine400 interconnecting the macro structure 200 with each micro node 300.FIG. 5 discloses an embodiment of the control facility which will befurther described below.

In addition to the above disclosed warehouse facility 210 and hydrationfacility 220, the macro structure 200 may also provide utilities to themanufacturing system 100. Such utilities may be provided to the micronodes 300 by means of the network spine 400.

According to another aspect of the disclosure, the macro structure 200may comprise administrative facilities and support facilities such aslaboratories, e.g., quality control laboratories. The researchfacilities could be segregated per micro node 300 operator, but stillprovided as a common good belonging to the macro structure 200.

Other facilities foreseen as part of the macro structure 200 arecafeteria areas, training areas, meeting rooms and parking spaces.Accordingly, the proposed manufacturing system 100 provides a costeffective solution for manufacturing a plurality of biopharmaceuticalproducts while maintaining full control of process separation and allquality requirements.

Turning to the micro nodes, FIG. 2 discloses an example scenario whereinthe manufacturing system 100 is brought into operation with two micronodes 300 a, 300 b. A third and fourth micro node 300 c and 300 d areprepared to be brought into operation, while further micro nodes (notshown) may be installed at a later time, retrofitted to themanufacturing system 100. The biopharmaceutical manufacturing may beconfigured for at least biosafety level 1, BSL-1 criteria and productionrequirements wherein harvest occurs every 3-4 days.

Each micro node 300 comprises biopharmaceutical manufacturing facilitiesand may be managed separately by respective operators. According toaspects of the disclosure, each micro node 300 is supported by the macrostructure 200 by means of the network spine 400 and is self-sufficientand independent of the other micro nodes. The micro node may also beinter-operationally discrete from the other micro nodes. Considering onemicro node 300 a of FIG. 2, the micro node is interconnected to themacro structure by means of the network spine 400. A communicationinterface 410 may provide inter-connectivity between the micro node 300a and the network spine 400. The communications interface may comprise adata interface 411 and/or a materials delivery interface 412, e.g., amaterials air lock. According to an aspect of the disclosure, the micronode 300 a also comprises a control unit 300 a 1, independent of thecontrol facility within the macro structure. The control unit of themicro node provides control of operations within the micro node. Afurther communications interface, controlled by the control unit 300 a1, is arranged to enable communication between the micro node 300 a anda public area. Such communication may involve entering of humanresources, employees, to the micro node 300 a from a public area, butalso data traffic to/from the micro node 300 a and an external network.

FIG. 3 is a flowchart illustrating various processes and procedures thatmay be completed in a macro structure in a manufacturing systemaccording to embodiments of the present invention. The macro structurereceives S31, in the control facility of the macro structure, a requestfor customized culture media and/or buffer. The request is processedwithin the control facility and submitted in an order to the hydrationfacility, e.g., in an automated manner. In the hydration facility, theculture media and/or buffer is customized S32 according to the receivedorder from the control facility. When the customization procedure hasbeen concluded, delivery S33 of the customized culture media and/orbuffer to the micro node is initiated in response to an order from thecontrol facility. Delivery takes place by means of the network spine,and may be performed in single-use equipment, e.g., by automated guidedvehicles in a fully automated manner.

Turning to FIG. 4, a flowchart illustrating various processes andprocedures that may be completed in a micro node in a manufacturingsystem according to embodiments of the present invention is illustrated.The micro node obtains S41 supply material comprising customized culturemedia. The supply material is processed S42 to produce respectivebiopharmaceutical products. Arriving at a quality assuredbiopharmaceutical product, the micro node initiates transfer S43 of thebiopharmaceutical drug to the macro structure, i.e., to the warehousefacility 210 for storage or delivery to an end user distributor. Asdisclosed in FIG. 3, the macro structure, receives S34 one or morefinalized biopharmaceutical products from the respective micro nodes,where physical receipt of the product follows upon receipt of a pick-uprequest sent to the control facility 230 of the macro structure 200. Thecontrol facility receiving the pick-up request, makes arrangements forsuch pick-up using the network spine for delivery of thebiopharmaceutical product from a network spine to the receivingwarehouse facility 210, e.g., by using automated guided vehicles in thenetwork spine. Manual delivery may also be used since the final productmay only consist of a small amount.

FIG. 5 shows a schematic diagram of an example control facility 230 ofthe macro structure 200. The control facility 230 is configured tocontrol interoperability of the macro structure 200 and the micro nodes300 by means of a network spine 400 interconnecting the macro structure200 with each micro node 300. The control facility comprises a memory231, processing circuitry 232, and input device 233. The controlfacility may also comprise a data interface 411 providing dataconnectivity with the network spine 400. As disclosed in FIG. 5, theprocessing circuitry may comprise micro node dedicated partitions 232a-232 d.

In general, the term processing circuitry may refer to, for example, oneor more computers, computing entities, distributed systems, processingdevices, processing entities, and/or any combination of devices orentities adapted to perform the functions, operations, and/or processesdescribed herein. Such functions, operations, and/or processes mayinclude, for example, transmitting, receiving, operating on, processing,storing, creating/generating, and/or similar terms used herein.

The control facility 230 is configured to execute a computer programproduct comprising at least one non-transitory computer readable storagemedium having computer-executable program code instructions storetherein. When executing the program code instructions in the processingcircuitry 232, the macro structure 200 is configured to controlinterconnectivity between the macro structure 200 and the micro nodes300 over the network spine 400 as discussed above. The control facilityis configured to receive a request for customized culture media and tocontrol customization of the culture media in the hydration facility.When the customization procedure has been concluded, the controlfacility initiates delivery of the customized culture media to the micronode Delivery takes place by means of the network spine, and may beperformed in single-use equipment, e.g., by automated guided vehicles ina fully automated manner. Following manufacturing of thebiopharmaceutical product in the micro node, the control facility mayreceive a pick-up request. Arrangements are made for such pick-up usingthe network spine for delivery of the biopharmaceutical product from anetwork spine to the receiving warehouse facility, e.g., by usingautomated guided vehicles in the network spine.

In the drawings and specification, there have been disclosed exemplaryaspects of the disclosure. However, many variations and modificationscan be made to these aspects without substantially departing from theprinciples of the present disclosure. Thus, the disclosure should beregarded as illustrative rather than restrictive, and not as beinglimited to the particular aspects discussed above. Accordingly, althoughspecific terms are employed, they are used in a generic and descriptivesense only and not for purposes of limitation.

The description of the example embodiments provided herein have beenpresented for purposes of illustration. The description is not intendedto be exhaustive or to limit example embodiments to the precise formdisclosed, and modifications and variations are possible in light of theabove teachings or may be acquired from practice of various alternativesto the provided embodiments. The examples discussed herein were chosenand described in order to explain the principles and the nature ofvarious example embodiments and its practical application to enable oneskilled in the art to utilize the example embodiments in various mannersand with various modifications as are suited to the particular usecontemplated.

In the drawings and detailed description, there have been disclosedexemplary embodiments. However, many variations and modifications can bemade to these embodiments. Accordingly, although specific terms areemployed, they are used in a generic and descriptive sense only and notfor purposes of limitation, the scope of the embodiments being definedby the following claims.

The invention claimed is:
 1. A method for quality assured manufacturingof at least two biopharmaceutical products in a manufacturing system,the manufacturing system comprising: a macro structure, at least twomicro nodes and a network spine interconnecting the macro structure witheach micro node, the macro structure comprising a warehouse facility anda hydration facility, and the at least two micro nodes representinginter-operationally discrete biopharmaceutical manufacturing facilities,wherein the macro structure and each micro node respectively eachcomprise a communication interface to the network spine, wherein thecommunication interface comprises a data interface arranged to receiveculture media and/or buffer orders from at least one of the micro nodesand to return a materials delivery to the micro node in response to thereceived order, wherein verification of the materials delivery isperformed prior to enabling delivery over a materials deliveryinterface, wherein a control facility in the macro structure isconfigured to control interoperability of the macro structure and themicro nodes by means of the network spine, the method comprising:receiving, in the control facility of the macro structure, a request forcustomized culture media and/or buffer; customizing culture media and/orbuffer in the hydration facility in response to an order from thecontrol facility; and delivering the customized culture media and/orbuffer to the requesting micro node in response to an order from thecontrol facility.
 2. The method of claim 1, further comprising:receiving one or more at finalized biopharmaceutical products from eachrespective micro node in a warehouse facility of the macro structure. 3.A method for quality assured manufacturing of at least twobiopharmaceutical products in a manufacturing system, the manufacturingsystem comprising: a macro structure, at least two micro nodes and anetwork spine interconnecting the macro structure with each micro node,the macro structure comprising a warehouse facility and a hydrationfacility, and the at least two micro nodes representinginter-operationally discrete biopharmaceutical manufacturing facilities,wherein the macro structure and each micro node respectively eachcomprise a communication interface to the network spine, wherein thecommunication interface comprises a data interface arranged to receiveculture media and/or buffer orders from at least one of the micro nodesand to return a materials delivery to the micro node in response to thereceived order, wherein verification of the materials delivery isperformed prior to enabling delivery over a materials deliveryinterface, wherein a control facility in the macro structure isconfigured to control interoperability of the macro structure and themicro nodes by means of the network spine, the method comprising:obtaining, in the respective micro nodes, supply materials comprisingcustomized culture media and/or buffer from the macro structure by meansof the network spine; and processing, in each micro node, the supplymaterials to produce respective biopharmaceutical products.
 4. Themethod of claim 3, further comprising: transferring, from eachrespective micro node, the biopharmaceutical product, to the macrostructure by means of the network spine.
 5. A manufacturing system forquality assured manufacturing of at least two biopharmaceuticalproducts, the manufacturing system comprising: a warehouse facility, ahydration facility, and at least two biopharmaceutical manufacturingfacilities, wherein the warehouse facility and hydration facility arecomprised in the macro structure, each biopharmaceutical manufacturingfacility is comprised in a respective micro node, and a controlfacility, having a hardware processor, in the macro structure isconfigured to control interoperability of the macro structure and themicro nodes by means of a network spine interconnecting the macrostructure with each micro node, wherein the macro structure and eachmicro node respectively each comprise a communication interface to thenetwork spine, wherein the communication interface comprises a datainterface arranged to receive culture media and/or buffer orders from atleast one of the micro nodes and to return a materials delivery to themicro node in response to the received order, wherein verification ofthe materials delivery is performed prior to enabling delivery over amaterials delivery interface.
 6. The manufacturing system of claim 5,wherein each micro node is supported by the macro structure by means ofthe network spine and is self-sufficient and independent of the othermicro nodes.
 7. The manufacturing system of claim 6, wherein each micronode is inter-operationally discrete from the other micro nodes.
 8. Themanufacturing system of claim 5, wherein each micro node comprises astand-alone control unit.
 9. The manufacturing system of claim 5,wherein the communication interface comprises the materials deliveryinterface.
 10. The manufacturing system of claim 9, wherein thematerials delivery interface is a materials air lock.
 11. Themanufacturing system of claim 9, further comprising automated guidedvehicles arranged for materials delivery between the macro structure andthe micro nodes.
 12. The manufacturing system of claim 9, wherein thematerials delivery comprise supply material delivered to a designatedmicro node in single-use equipment, the supply material comprisingcustomized culture media and/or buffer.
 13. The manufacturing system ofclaim 9, wherein the micro nodes are arranged to receive materialsdelivery of single-use product contact components.
 14. The manufacturingsystem of claim 5, wherein the network spine is preconfigured forretrofit connection of one or more further micro nodes.
 15. Themanufacturing system of claim 5, wherein each micro node comprises afurther communication interface controlled by the stand-alone controlunit, wherein the further communications interface is arranged tocontrol communication between the micro node and a public area.
 16. Acomputer program product comprising: at least one non-transitorycomputer readable storage medium having computer-executable program codeinstructions store therein, the computer-executable program codeinstructions comprising program code instructions configured to, whenexecuted in a control facility of a macro structure: receive, from amicro node, a request for supply material, wherein the supply materialcomprises customized culture media; and control, in a hydration facilityof the macro structure, preparation of the customized culture media,wherein the macro structure and the micro node respectively eachcomprise a communication interface to a network spine, wherein thecommunication interface comprises a data interface arranged to receiveculture media and/or buffer orders from the micro node and to return amaterials delivery to the micro node in response to the received order,wherein verification of the materials delivery is performed prior toenabling delivery over a materials delivery interface.